This is a proposal to examine the synaptic interactions between neurons containing major transmitters in the hippocampal formation and the septal complex in three separate but interrelated studies. In Studies I and II we propose to determine the synaptic relations and septal origin of cholinergic and GABAergic terminals in the hippocampal formation. Specifically, synaptic relations first will be examined with respect to all types of hippocampal neurons and subsequently with respect to known intrinsic transmitters such as GABA and the neuropeptides, somatostatin and neuropeptide Y. The same terminals will also be examined with respect to other subcortical afferents from monoaminergic neurons identified by tyrosine hydroxylase and 5- hydroxytryptamine. Study III proposes to examine the synaptic relations between monoaminergic afferents and (1) septohippocampal neurons identified by retrograde transport of horseradish peroxidase following injections into the hippocampal formation, or (2) septal neurons identified by immunoreactivity for choline acetyltransferase or GABA. The primary methods to be used in these studies are electron microscopic (1) immunocytochemistry with peroxidase, gold and radioiodinated markers for identification of one or more antigens in single sections of tissue and (2) transport with amino acids, horseradish peroxidase or plant lectins for identification of neuronal pathways. The results from the three studies should be complimentary and broaden our knowledge of interactions between transmitter specific septohippocampal neurons and their relation to monoaminergic afferents. The studies will be carried out in adult male rats, but should provide basic information on the neuronal circuitry within regions known to be important for specific memory disorders in man.